Circulating TGF-β and SMAD3 in relation to early fibrotic lung changes and pulmonary function in pulmonary tuberculosis: A prospective cohort study

BACKGROUND: Early structural lung remodeling may develop during pulmonary tuberculosis (TB) treatment, but its relationship with circulating mediators of fibrotic signaling remains poorly characterized. We investigated circulating transforming growth factor-beta (TGF-β) and SMAD3 in relation to early radiological fibrotic changes and pulmonary function. METHODS: In this prospective cohort study, 38 adults with newly diagnosed pulmonary TB completed two months of standard intensive-phase treatment. Serum TGF-β and SMAD3 were measured by ELISA, while radiological fibrosis severity and pulmonary function were assessed after the intensive phase. Between-group differences and associations with fibrosis severity were evaluated using appropriate parametric and non-parametric analyses. RESULTS: Early radiological fibrotic changes were identified in 31/38 participants (81.6%). FVC and FEV1 were numerically lower with greater fibrosis severity, although overall between-group differences were not significant (p = 0.145 and p = 0.213, respectively). Fibrosis severity was inversely correlated with FVC (ρ = -0.388, p = 0.016) and FEV1 (ρ = -0.341, p = 0.036). Circulating TGF-β did not differ significantly across fibrosis categories (p = 0.179). In contrast, SMAD3 differed across categories (p = 0.035) and correlated with fibrosis severity (ρ = 0.483, p = 0.002); after Holm adjustment, only the no-fibrosis versus severe-fibrosis comparison remained significant (p = 0.025). CONCLUSIONS: Circulating SMAD3, but not TGF-β, was associated with early radiological fibrosis severity during TB treatment. These findings support further longitudinal investigation of molecular changes accompanying post-TB pulmonary remodeling without establishing pathway activation or clinical biomarker utility.